PROJECT ABSTRACT As part of the parent grant, R01MH110051, IPrEP: A Combination HIV Prevention Strategy for Young Women at Risk for HIV, we conducted formative research among young female sex workers (FSW) and male clients (MC) and will shortly initiate a randomized controlled trial comparing the feasibility, acceptability and effectiveness of two adherence support interventions for young FSW prescribed oral HIV PrEP. However, no PrEP intervention is included for MC in the parent study. MC are an integral part of sex work-driven HIV transmission dynamics and a potential bridging population to their FSW and non-FSW partners. MC who have unprotected sex with FSW are at risk of HIV and other sexually transmitted infections (STI), yet they are understudied and underserved. They are seldom the target of HIV prevention programming, including for pre- exposure prophylaxis, an efficacious prevention intervention. Thus, interventions that address the web of HIV transmission linking FSW, MC and other sexual partners are needed to strengthen the impact of combination prevention strategies and the effectiveness of the scale up of HIV prevention efforts by PEPFAR. In response, we propose to assess the feasibility and acceptability of a PrEP-focused prevention strategy, using daily oral tenofovir/emtricitabine (TDF/FTC) in combination with a self-management approach aimed at enhancing adherence, tailored to the MC population (PrEP+ strategy). The project has two sequential components including (1) a cross-sectional survey and HIV testing to identify structural, psychosocial, behavioral and demographic correlates of HIV infection and elucidate contexts of HIV risk behavior, HIV testing, and PrEP knowledge, attitudes and intentions in a sample of 200 MC and (2) Enrollment of a PrEP+ MC cohort to evaluate adherence, feasibility, and acceptability of a combination PrEP strategy aimed at strengthening PrEP adherence in a cohort of 60 MC. MC will receive daily oral tenofovir/emtricitabine (TDF/FTC) in combination with adherence self- management interventions including: point-of-care urine test to measure PrEP antiretroviral (ARV) drug levels for adherence in participant urine samples over the preceding seven days and give feedback and tailored counseling based on urine test results; provision of HIV self-test (HIVST) kits to confirm their HIV-negative status and make a connection between PrEP use and protection against HIV and; 2-way standard text messaging to send periodic adherence reminders. Findings from this pilot research will inform PEPFAR's efforts to implement and scale-up PrEP among this population at risk for HIV acquisition. The proposed research will also identify factors that account for engagement in or discontinuation of PrEP. The ultimate goal is the identification of new approaches for PEPFAR to effectively engage men at risk of HIV and enable them to remain HIV-free through the use of PrEP, for their own health and to prevent onward transmission of HIV to their partners.